Skip to main content
SpringerLink
Log in

Pharmacokinetics of ketorolac tromethamine compression-coated tablets for colon delivery

  • Clinical Research
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Present research efforts are focused in developing compression-coated ketorolac tromethamine tablets to improve the drug levels in colon by retarding the drug release in the stomach and small intestine. To achieve this objective, core tablets containing ketorolac tromethamine were prepared by direct compression and compression coated with sodium alginate. The developed tablets were evaluated for physical properties, in vitro drug release, X-ray imaging, and pharmacokinetic studies in human volunteers. Based on the in vitro drug release study, the optimized formulation showed very little drug release (6.75 ± 0.49 %) in the initial lag period of 5 h, followed by progressive release up to 97.47 ± 0.93 % within 24 h. The X-ray imaging of tablets in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. From the pharmacokinetic study, the C max of colon-targeted tablets was 3,486.70 ng/ml at T max 10 h, whereas in the case of immediate-release tablets, the C max of 4,506.31 ng/ml at T max 2 h signifies the ability of compression-coated tablets to target the colon. In conclusion, compression-coated tablets are suitable to deliver ketorolac tromethamine to the colon.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Vincent HL, Suman KM. Drug delivery-oral colon-specific. In: Swarbick J, Boylan CJ, editors. Encyclopedia of pharmaceutical technology. New York: Marcel Dekker; 2002. p. 871–85.

    Google Scholar 

  2. Krishnaiah YSR, Satyanarayana S, Ramaprasad YV, Narasimharao S. Evaluation of guar gum as a compression coat for drug targeting to colon. Int J Pharm. 1998;171:137–46.

    Article  CAS  Google Scholar 

  3. Maroni A, Zema L, Curto MDD, Foppoli A, Gazzaniga A. Oral colon delivery of insulin with the aid of functional adjuvants. Adv Drug Deliv Rev. 2012;64:540–56.

    Article  CAS  PubMed  Google Scholar 

  4. Vemula SK, Veerareddy PR. Different approaches to design and evaluation of colon specific drug delivery systems. Int J Pharm Technol. 2009;1(1):1–35.

    CAS  Google Scholar 

  5. Asghar LF, Chandran S. Multiparticulate formulation approach to colon-specific drug delivery: current perspectives. J Pharm Sci. 2006;9(3):327–38.

    CAS  Google Scholar 

  6. Kumar M, Ali A, Kaldhone P, Shirode A, Kadam VJ. Platform technologies for colon targeted drug delivery system. J Pharm Res. 2010;3(3):543–7.

    CAS  Google Scholar 

  7. Aurora J, Talwar N, Pathak V, Colonic drug delivery challenges and opportunities—an overview. Eur Gastro Rev. 2006;1–6.

  8. Cheng G, Feng A, Zou M. Time and pH dependent colon specific drug delivery for orally administered diclofencac sodium and 5-amino salicylic acid. World J Gastroenterol. 2004;10(12):1769–74.

    CAS  PubMed  Google Scholar 

  9. Sinha VR, Bhinje JR, Kumaria R, Kumar M. Development of pulsatile systems for targeted drug delivery of celecoxib for prophylaxis of colorectal cancer. Drug Deliv. 2006;13:221–5.

    Article  CAS  PubMed  Google Scholar 

  10. Wu B, Shun N, Wei X, Wu W. Characterization of 5-fluorouracil release from hydroxypropyl methylcellulose compression-coated tablets. Pharm Dev Technol. 2007;12:203–10.

    Article  CAS  PubMed  Google Scholar 

  11. Veerareddy PR, Vemula SK. Formulation, evaluation and pharmacokinetics of colon targeted pulsatile system of flurboprofen. J Drug Target. 2012;20(8):703–14.

    Article  CAS  PubMed  Google Scholar 

  12. Chickpetty SM, Baswaraj R, Nanjwade BK. Studies on development of novel combined time and pH dependent solventless compression coated delivery systems for colonic delivery of diclofenac sodium. Asian J Pharm Clin Res. 2010;3(2):110–3.

    CAS  Google Scholar 

  13. Maroni A, Curto MDD, Serratoni M, Zema L, Foppoli A, Gazzaniga A, et al. Feasibility, stability and release performance of a time-dependent insulin delivery system intended for oral colon release. Eur J Pharm Biopharm. 2009;72:246–51.

    Article  CAS  PubMed  Google Scholar 

  14. Srivastava R, Kumar D, Pathak K. Colonic luminal surface retention of meloxicam microsponges delivered by erosion based colon-targeted matrix tablet. Int J Pharm. 2012;427:153–62.

    Article  CAS  PubMed  Google Scholar 

  15. Makhlof A, Tozuka Y, Takeuchi H. pH-sensitive nanospheres for colon-specific drug delivery in experimentally induced colitis rat model. Eur J Pharm Biopharm. 2009;72:1–8.

    Article  CAS  PubMed  Google Scholar 

  16. Asghar LF, Chure CB, Chandran S. Colon specific delivery of indomethacin: effect of incorporating pH sensitive polymers in xanthan gum compression coated bases. AAPS Pharm Sci Technol. 2009;10(2):418–29.

    Article  CAS  Google Scholar 

  17. Hashem FM, Shaker DS, Nasr M, Saad IE, Ragaey R. Guar gum and hydroxy propyl methylcellulose compressed coated tablets for colonic drug delivery: in vitro and in vivo evaluation in healthy human volunteers. Drug Discov Ther. 2011;5:90–5.

    CAS  PubMed  Google Scholar 

  18. Mandal S, Basu SK, Sa B. Ca2+ ion cross-linked interpenetrating network matrix tablets of polyacrylamide-grafted-sodium alginate and sodium alginate for sustained release of diltiazem hydrochloride. Carbohydr Polym. 2010;82:867–73.

    Article  CAS  Google Scholar 

  19. Brahmankar DM, Karwa RM, Jaiswal SB. Cellulose matrix for controlled release of keterolac tromethamine. India Drugs. 1996;33(3):120–3.

    CAS  Google Scholar 

  20. Chopra D, Sinha VR, Singh M. Thermal and isothermal methods in development of sustained release dosage forms of ketorolac tromethamine. Eur J Chem. 2008;5(2):316–22.

    CAS  Google Scholar 

  21. El-Kamel AH, Abdel-Aziz AM, Fatani AJ, El-Subbagh HI. Oral colon targeted delivery systems for treatment of inflammatory bowel diseases: synthesis, in vitro and in vivo assessment. Int J Pharm. 2008;358:248–55.

    Article  CAS  PubMed  Google Scholar 

  22. Vemula SK, Veerareddy PR. Formulation, evaluation and pharmacokinetics of ketorolac tromethamine time-dependent colon targeted drug delivery system. Exp Opin Drug Deliv. 2013;10(1):33–45.

    Article  CAS  Google Scholar 

  23. Wu B, Shun N, Wei X, Lu Y, Wu W. Biphasic release of indomethacin from HPMC/pectin/calcium compression coated tablet: I. Characterization and mechanistic study. Eur J Pharm Biopharm. 2007;67:707–14.

    Article  CAS  PubMed  Google Scholar 

  24. Valluru R, Siddaramaiah T, Pramod M. Influence of natural polymer coating on novel colon targeting drug delivery system. J Mater Sci. 2008;19:2131–6.

    Google Scholar 

  25. Talukder RM, Fassihi R. Development and in-vitro evaluation of a colon-specific controlled release drug delivery system. J Pharm Pharmacol. 2008;60:1297–303.

    Article  CAS  PubMed  Google Scholar 

  26. Chaudhary A, Tiwari N, Jain V, Singh R. Microporous bilayer osmotic tablet for colon-specific delivery. Eur J Pharm Biopharm. 2011;78:134–40.

    Article  CAS  PubMed  Google Scholar 

  27. Mathews BR. Regulatory aspects of stability testing in Europe. Drug Dev Ind Pharm. 1999;25:831–56.

    Article  Google Scholar 

  28. Tugcu-Demiroz F, Acarturk F, Takka S, Konus-Boyunaga O. In vitro and in vivo evaluation of mesalazine-guar gum matrix tablets for colonic drug delivery. J Drug Target. 2004;12:105–12.

    Article  PubMed  Google Scholar 

  29. Vemula SK, Veerareddy PR. Formulation and evaluation of ketorolac tromethamine tablets for time and pH dependent colon specific delivery. J Curr Pharm Res. 2011;8(1):31–9.

    Google Scholar 

  30. Ashford M, Fell J, Attwood D, Sharma H, Woodhead P. An evaluation of pectin as a carrier for drug targeting to the colon. J Control Release. 2003;26:213–20.

    Article  Google Scholar 

  31. Ghimire M, Hodges LA, Band J, Lindsay B, Mahony BO, McInnes FJ, et al. Correlation between in vitro and in vivo erosion behaviour of erodible tablets using gamma scintigraphy. Eur J Pharm Biopharm. 2011;77:148–57.

    Article  CAS  PubMed  Google Scholar 

  32. Grahnen A. Design of bioavailability studies. Pharm Int. 1984;5:100–3.

    CAS  Google Scholar 

  33. Krishnaiah YSR, Raju VP, Kumar DB, Satyanarayana V, Karthikeyan RS, Bhaskar P. Pharmacokinetic evaluation of guar gum-based colon-targeted drug delivery systems of mebendazole in healthy volunteers. J Control Release. 2003;88:95–103.

    Article  CAS  PubMed  Google Scholar 

  34. Krishnaiah YSR, Satyanarayana S, Dinesh Kumar B, Karthikeyan RS, Bhaskar P. In vivo pharmacokinetics in human volunteers: oral administered guar gum-based colon-targeted 5-fluorouracil tablets. Eur J Pharm Sci. 2003;19:355–62.

    Article  CAS  PubMed  Google Scholar 

  35. Vyas SP, Roop KK. Controlled drug delivery concepts and advances. Delhi: Vallabh Prakashan Publishers; 1999. p. 218–56.

    Google Scholar 

Download references

Acknowledgments

The authors acknowledge Bright Labs, Hyderabad, India and Matrix Laboratories, Hyderabad, India for the gift sample of ketorolac tromethamine and sodium alginate. The authors also thank the Principal and Management, Jangaon Institute of Pharmaceutical Sciences for providing facilities.

Conflict of interest

The authors report no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, Chaitanya College of Pharmacy Education and Research, Kishanpura, Hanamkonda, Warangal, Andhra Pradesh, 506001, India

    Sateesh Kumar Vemula, Prabhakar Reddy Veerareddy & Venkat Ratnam Devadasu

  2. Department of Pharmaceutics, Jangaon Institute of Pharmaceutical Sciences, Yeshwanthapur, Jangaon, Warangal, Andhra Pradesh, 506167, India

    Sateesh Kumar Vemula

  3. College of Pharmacy, Palamuru University, Mahabubnagar, Andhra Pradesh, India

    Prabhakar Reddy Veerareddy

Authors
  1. Sateesh Kumar Vemula
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prabhakar Reddy Veerareddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Venkat Ratnam Devadasu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sateesh Kumar Vemula.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vemula, S.K., Veerareddy, P.R. & Devadasu, V.R. Pharmacokinetics of ketorolac tromethamine compression-coated tablets for colon delivery. Drug Deliv. and Transl. Res. 4, 310–319 (2014). https://doi.org/10.1007/s13346-014-0195-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-014-0195-x

Keywords

Search

Navigation